The generic term “back pain” comprises a wide range of disorders, whose definition is often uncertain and whose etiology is difficult to classify, characterised by a common symptom: “backache”. The lumbosacral section of the spinal column is a crucial structure; of all the transitional hinges, it is certainly the one that comes under most stress, but is also the most mobile, which exposes it to continual overloads and imbalances. The focal point of the spinal column is the intervertebral disc. It is contained between all types of vertebrae, and comprises two concentric sub-structures: the external annulus fibrosus, which surrounds the internal nucleus pulposus. The annulus fibrosus is a stratified elastic tissue consisting of extracellular matrix enriched with a series of protein fibres (mainly type II collagen) arranged in a zigzag pattern, i.e. not vertically oriented. Specifically, the ring consists externally of type I collagen fibres (known as Sharpey's fibres), while the central part consists of type II collagen and chondrocytes. The nucleus pulposus is a gelatinous tissue mainly consisting of water (about 85% in volume in healthy young people), imbibed by a proteoglycan matrix (mostly consisting of hyaluronate, chondroitin and keratan sulphate) produced by the chondrocytes that reside in the innermost part of the annulus fibrosus. The nucleus pulposus acts as a bearing, which supports and distributes the compressive forces to which the spinal column is continually subjected; the annulus fibrosus supports the tensile forces and provides mechanical support and stability for the spine. The intervertebral disc is an avascular structure, which obtains its nourishment from the blood vessels that supply the adjacent bone structures.
As a result of microtraumas, or more simply advancing age, especially at lumbosacral level, the intervertebral disc undergoes structural modifications that give rise to the disorder known as “intervertebral disc degeneration” (Yong-Soo, Asian Spine Journal, 2009, 3, 39-44). It involves a set of complex phenomena, whose etiology is not always uniform, and which has different clinical characteristics. It ranges from asymptomatic degeneration, found in younger people, to particularly painful forms complicated by major postural alterations. The latter usually (but not always) occur in elderly people, and can be caused by trauma, wear and tear, malnutrition or simply, as stated, aging of the structures that make up the intervertebral disc. The various forms of intervertebral disc degeneration include one characterised by a reduction in water content, leading to a reduction in and modification of the structure of the proteins and proteoglycans that make up the nucleus pulposus; it becomes dehydrated, empties, and loses its gelatinous structure and the clear demarcation from the annulus fibrosus. The degenerative alteration of the disc is clearly shown on NMR scans; it appears globally thinner than healthy discs and shows a change of colour to various shades of black, due to the reduction in the water content of the nucleus pulposus. This pathological situation is known as black disc disease. The thinning, as well as reducing the ability of the disc to absorb shocks and provide stability for the spine, is nearly always accompanied by the release of inflammatory factors, which generate intense pain (Rengachary et al., Neurosurg Focus, 2002, 13, E14).
In the later stages of disc disease, the nucleus pulposus may also press on the annulus fibrosus (“bulging”), which may rupture, giving rise to a hernia.
In less serious cases, a conservative approach is taken, based on physiotherapy associated with pain control, as the pain is very acute and disabling. As the classic painkillers have little or no effect, treatment with ozone, administered by injection, has been successfully used for some time; this treatment exploits the powerful antioxidant, anti-inflammatory and therefore painkilling action of ozone.
In the most serious cases, in addition to pain control, strategies which are effective from the functional standpoint and are curative of black disc disease are sought, i.e. strategies which at least partly reduce the cause, and restore the structure and functionality of the nucleus pulposus. In the vast majority of cases black disc disease is accompanied by postural defects, which in turn generate further stiffness and pain.
One approach is to administer cells able to produce proteoglycan matrix, such as mesenchymal stem cells from bone marrow, possibly combined with molecules that promote the formation of matrix by the residual cells (such as growth factors) and with inflammatory cytokine inhibitors, into the nucleus pulposus. This approach attempts to restore the proteoglycan matrix and to control the pain.
However, these treatments are still experimental, and require thorough verification, because they are particularly problematic (as regards the number of cells to be used, the active substances and their concentrations and the type of carrier, for example). However, the usefulness of administering cells to the nucleus pulposus is somewhat controversial; as previously stated, this structure does not originally contain cells, and is avascular, which means that the proliferation of the cells introduced depends on the blood supply of the surrounding structures, which is sure to be impaired in pathological situations.
The technique that involves introducing into the nucleus pulposus a “bearing” able to absorb and distribute compressions, thus recreating a condition similar to the physiological condition, is much more promising.
The Applicant has found and demonstrated that a “bearing” consisting of a hydrogel with the following characteristics is particularly suitable for this type of application:                it can be implanted by minimally invasive, preferably injectable techniques, and is therefore easily extrudable;        it remains in situ without slipping away from the site of implantation because it has precise rheological characteristics;        it possesses mechanical properties (elasticity, compressibility) suitable to support and redistribute compressions;        it is highly hydratable;        it is absolutely safe, both in its unmodified form and as degradation products, inevitably originating from physiological enzyme activity.        
The hydrogel whose efficacy is demonstrated by the Applicant below consists of a hyaluronic acid derivative. Hyaluronic acid (HA) is a linear-chain heteropolysaccharide consisting of alternating residues of D-glucuronic acid and N-acetyl-D-glucosamine. It is present in nature in pericellular gels, in the ground substance of the connective tissue of vertebrates (of which it is one of the main constituents), in the synovial fluid of the joints, and in the vitreous humour and umbilical cord. HA therefore plays an important role in the biological organism, both as a mechanical support for the cells of many tissues, such as skin, tendons, muscles and cartilage, and as a viscous fluid that absorbs shocks and ensures that the joint surfaces can slide over one another.
Native hyaluronic acid has an extremely variable average molecular weight (MW), depending on the source from which it is obtained and the preparation methods used, ranging from 50 to 13×106 Da.
It should be noted that “average molecular weight” here means the weight-average molecular weight, calculated by the “intrinsic viscosity” method (Terbojevich et al., Carbohydr Res, 1986, 363-377).
One of the fundamental characteristics of HA is that it can be variously modified from the chemical standpoint, to transform its rheological and mechanical characteristics while maintaining its biological characteristics unchanged.
The Applicant has surprisingly found that of the numerous HA derivatives known to the prior art (esters, N- and O-sulphated derivatives, inner esters, etc.), the most suitable for the application described here are those obtained by formation of an amide bond between the carboxyl of the glucuronic acid residue and the hexadecylamine. The Applicant has also demonstrated that these derivatives not only cause a considerable reduction in pain symptoms, evaluated by comparison with the ozone treatment conventionally used in black disc disease, but also produce a wholly unforeseeable functional improvement.